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Publications

Journal Article Epublish

PubMed: 42926845 DOI: 10.1016/j.isci.2026.117881

Design and validation of a GMP-compliant manufacturing platform of extracellular vesicles from mesenchymal stromal cells.

iScience 29(11):117881

Authors: Yvan Courageux, Marta Monguió-Tortajada, Alba López-Fernández, Leonie Schoch, Francesc Poblador, Sara Morini, Cristina Prat-Vidal, Luciano Rodriguez, Silvia Torrents, Gemma Aran, Margarita Codinach, Carolina Gálvez-Montón, Antoni Bayes-Genis, Joaquim Vives, Sergi Querol, Santiago Roura

Affiliations

  • ICREC Research Program, Health Science Research Institute Germans Trias i Pujol, Can Ruti Campus, Badalona, Spain. Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Bellaterra, Spain.
  • Department of Immunobiology, University of Lausanne, 1066 Epalinges, Switzerland.
  • Banc de Sang i Teixits, Barcelona, Spain. Musculoskeletal Tissue Engineering Group, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
  • ICREC Research Program, Health Science Research Institute Germans Trias i Pujol, Can Ruti Campus, Badalona, Spain.
  • Banc de Sang i Teixits, Barcelona, Spain.
  • Transfusion Medicine Group, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
  • ICREC Research Program, Health Science Research Institute Germans Trias i Pujol, Can Ruti Campus, Badalona, Spain. CIBERCV, Instituto de Salud Carlos III, Madrid, Spain. Heart Institute (iCor), Cardiology Service, Germans Trias i Pujol University Hospital, Badalona, Spain.
  • CIBERCV, Instituto de Salud Carlos III, Madrid, Spain.
  • Heart Institute (iCor), Cardiology Service, Germans Trias i Pujol University Hospital, Badalona, Spain.
  • Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Musculoskeletal Tissue Engineering Group, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
  • Spanish Bone Marrow Registry (REDMO), Barcelona, Spain.
  • ICREC Research Program, Health Science Research Institute Germans Trias i Pujol, Can Ruti Campus, Badalona, Spain. CIBERCV, Instituto de Salud Carlos III, Madrid, Spain. Heart Institute (iCor), Cardiology Service, Germans Trias i Pujol University Hospital, Badalona, Spain. Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), Vic/Manresa, Catalonia, Spain.

Abstract

There is growing interest in mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) as key components in the development of next-generation regenerative cell-free therapies; however, their clinical translation remains limited by a lack of validated clinical-grade manufacturing platforms. Thus, we have established a good manufacturing practice (GMP)-compliant, semi-automated, mid-scale manufacturing workflow that couples the single-use stirred-tank bioreactor expansion of Wharton's jelly-derived MSCs with tangential flow filtration and automated size-exclusion chromatography, featuring in-line monitoring of critical process parameters. The MSC-EV-based product meets pre-specified critical quality attributes (CQAs), co-expresses parental-cell- and EV-specific markers, and complies with standardized quality and safety regulations. Moreover, the final product CQAs-including CD73-associated immunomodulatory activity-remained within acceptable limits for 12 months of storage in PlasmaLyte 148 at -80°C. Overall, our integrated platform yields MSC-EVs with high batch-to-batch reproducibility, in alignment with current GMP and regulatory standards, thereby providing a robust foundation supporting their potential clinical applicability.

MeSH

Cells, Extracellular Vesicles, Mesenchymal Stem Cells, Bioreactors, Stromal Cells